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February 18, 2014
08:13 EDTMACKMerrimack MM-141 preclinical study published in Molecular Cancer Therapeutics
Merrimack Pharmaceuticals announced that the manuscript "MM-141, an IGF-1R- and ErbB3-Directed Bispecific Antibody, Overcomes Network Adaptations That Limit Activity of IGF-1R Inhibitors" has been published in Molecular Cancer Therapeutics and selected for the Highlights section in the current issue . This publication describes the preclinical development of Merrimack's MM-141, a novel bispecific tetravalent antibody that binds to IGF-1R and ErbB3 receptors. With this mechanism, MM-141 is able to inhibit oncogenic signaling through the PI3K/AKT/mTOR pathway, which is a driving force behind cell growth. MM-141 recently completed the monotherapy portion of a Phase 1 study in the United States and Europe. It is currently being investigated in a Phase 1 combination study and is expected to enter Phase 2 development in 2014. IGF-1R, the receptor activated by insulin-like growth factor 1, has the ability to induce cellular growth and proliferation. Thus, it has been implicated in promoting resistance to both chemotherapies and targeted therapies. However, the effectiveness of current IGF-1R inhibitors in the clinic has been limited, as cancer cells have the ability to develop resistance to therapies by signaling through alternative pathways. Through a systems biology-based methodology, Merrimack researchers have found that cancer cells can develop resistance to IGF-1R that is mediated through ErbB3. Therefore, dual inhibition of IGF-1R and ErbB3 pathways would be necessary to block the PI3K/AKT/mTOR pathway, resulting in the arrest of tumor cell growth. In preclinical in vitro and in vivo models, MM-141 was more active than a combination of anti-ErbB3 and anti-IGF-1R monoclonal antibodies. MM-141 was able to inhibit PI3K/AKT/mTOR signaling and potentiated the activity of cytotoxic and targeted therapies, supporting its ongoing clinical development.
News For MACK From The Last 14 Days
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January 22, 2015
18:28 EDTMACKOn The Fly: After Hours Movers
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17:54 EDTMACKMerrimack Chief Scientific Officer Ulrik Nielsen resigns
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January 20, 2015
08:16 EDTMACKMerrimack data of Phase 3 MM-398 NAPOLI-1 study supports development programs
Merrimack Pharmaceuticals (MACK) announced that additional analyses were presented on January 16, 2015 from the Phase 3 NAPOLI-1 study of MM-398, also known as nal-IRI, in patients with metastatic pancreatic cancer previously treated with gemcitabine-based therapy. Merrimack and Baxter International's (BAX) biopharmaceutical business are collaborating on the development and commercialization of MM-398 outside of the United States and Taiwan. PharmaEngine holds the rights to commercialize MM-398 in Taiwan. Additionally, Merrimack presented preclinical and clinical data from studies of its investigational agents MM-141 and MM-151 in pancreatic and colorectal cancer, respectively. An investigator-sponsored study of MM-398 in colorectal cancer was also presented. The extended analyses for the global NAPOLI-1 Phase 3 trial presented at ASCO GI support the robustness of the overall survival benefit of MM-398 in combination with 5-fluorouracil, or 5-FU, and leucovorin presented in June 2014, at the European Society for Medical Oncology World Congress on Gastrointestinal Cancer, or ESMO GI. The primary analysis, presented at ESMO GI, demonstrated a statistically significant advantage in overall survival with an unstratified hazard ratio of 0.67, and a median of 6.1 months for the combination of MM-398 plus 5-FU and leucovorin compared to 4.2 months in the control arm.
January 15, 2015
07:59 EDTMACKAmerican Society of Clinical Oncology to hold a symposium
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January 14, 2015
07:37 EDTMACKJPMorgan to hold a conference
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